Introduction: Carbapenem-resistant Acinetobacter baumannii represents a global health problem due to its limited therapeutic options and high associated mortality. Cefiderocol, a novel siderophore cephalosporin derivated has emerged as a potential treatment for infections caused by multidrug resistant Gram-negative bacteria as Acinetobacter baumannii, however, its microbiological activity, clinical performance, and resistance patterns remain heterogeneous across different studies.

Objective: To synthesize and critically evaluate the available scientific evidence regarding the activity of cefiderocol against Acinetobacter baumannii, with particular emphasis on susceptibility profiles and clinical outcomes, including mortality.

Material and methods: A structured literature search was conducted in PubMed, Scopus and Cochrane data bases between the 2018 and 2025 period, where the primary search terms included “Acinetobacter baumannii” and “cefiderocol,” both as MeSH terms. After excluding non-relevant bacterial species, 61 articles were retrieved, of those, 18 studies were excluded for not meeting the predefined inclusion criteria. Consequently, 43 studies were included in the final narrative synthesis and qualitative analysis.

Results: The integrated evidence demonstrates that cefiderocol exhibits relevant in vitro activity against Acinetobacter baumannii. In vivo studies indicate that cefiderocol retains bactericidal activity against susceptible isolates and that combination therapy, particularly with ampicillin/sulbactam, may enhance antimicrobial efficacy. Clinical and observational evidence evaluating mortality was limited. The available observational study reported mortality rates comparable to those previously described for carbapenem-resistant Acinetobacter baumannii infections, with no statistically significant difference between cefiderocol monotherapy and combination therapy.

Conclusions: Cefiderocol demonstrates consistent in vitro and in vivo activity against Acinetobacter baumannii, including carbapenem-resistant and colistin-resistant isolates, however, clinical evidence evaluating mortality outcomes remains limited. Therefore, while cefiderocol represents a promising option for the treatment of Acinetobacter baumannii infections, its impact on mortality cannot be definitively established based on current evidence, highlighting the need for further clinical studies.